Eight research projects received IMPACT Awards (project duration: Jan. 2018 to Jan. 31, 2019).
Bariatric surgery is an evidence-based and cost effective medical treatment for severe obesity, with Roux-en-Y gastric bypass (RYGB) being the most common bariatric procedure performed. With more than 40% of postoperative bariatric patients (PBPs) experiencing excessive weight regain (i.e., 25%+ of total lost weight) and the majority of PBPs regaining some weight, we must better understand multi-modal factors contributing to uncontrolled or addictive eating behaviors and weight regain. Further, postoperative elevated risk for new-onset or relapse substance abuse and addiction transfer (food to substances) may impede surgical outcomes. Although mechanisms are unclear, postoperative neurobiological changes in brain signaling and changes in brain regions that control reward are associated with problematic eating behaviors. Further, those with genetic susceptibility to obesity are prone to difficulty regulating behaviors around triggering substances.
More information is needed in adult weight loss surgery populations: do surgical procedures affecting the gut-brain axis contribute to varied (a) brain responses to environmental cues and (b) surgical weight outcomes (i.e., success versus failure)? How might genetic variation help explain these outcomes? We will examine genetic profiles, psychosocial variables, and attentional bias to food and alcohol cues (via EEG signaling) in successful versus unsuccessful patients who underwent gastric bypass surgery. To date, no one has examined EEG signaling in post-operative bariatric patients. This project will inform precision interventions to ensure long-term weight loss and cost effective bariatric surgeries. Individualized, multi-component clinical protocols can be developed based on pre-surgical addiction status, genetic vulnerability, and other multi-modal profiling information.
Children’s school readiness skills pave the way for life success. School readiness includes familiar academic skills like alphabet knowledge; as well as cognitive and behavioral skills like self-control, attending to tasks and interactions, and remembering new information. This latter set of skills are together considered behavioral self-regulation, which is linked to a wide range of outcomes spanning from early childhood to adulthood. Similar to the children’s game, Simon Says, the Head-Toes-Knees-Shoulders (HTKS) assessment is a supported measure of behavioral self-regulation that predicts children’s academic achievement and classroom behavior from preschool through early elementary school.
The HTKS has been used in research studies across the United States and the world. Although robustly validated in research, norms that help translate the practical meaning of a HTKS score in relation to expected achievement or behavioral outcomes are not yet available. To aid use with different types of children and in non-research contexts, the proposed study will establish initial norms for the HTKS. Existing data sets with HTKS scores, academic achievement in mathematics and literacy, and social skills will be examined. The design of the study includes (Phase 1) gathering HTKS data from internal and external sources and analyzing data to establish initial norms for the measure; and (Phase 2) developing an external grant proposal and disseminating findings to scholars and practitioners. This study will initiate developing the HTKS as a normed school readiness assessment option, with implications for both scholars and practitioners who want to incorporate behavioral self regulation in school readiness efforts.
Kidney transplantation is the method of therapy preferred by patients on dialysis, yet only 20% of those nearly 600,000 patients nationwide are active on transplant waitlists. Access to the waitlist is further reduced for people of color, with African Americans less likely to: be referred to a transplant center; complete testing; be found eligible for the waitlist; and remain active once listed. African American end-stage renal disease (ESRD) patients are 24% less likely than white ESRD patients to receive a kidney transplant, denying them equitable access to the reduced mortality, increased quality of life, and lower health system costs associated with transplantation. Limited health literacy, affecting 30%-50% of ESRD patients nationally, is a compounding factor contributing to racial disparities in access to transplantation.
This study proposes to design and test three culturally sensitive animated videos, with information presented in a manner respectful of education and learning style needs, meant to increase health literacy and, consequently, the number of active kidney transplant wait-listings among African Americans who have been referred for transplantation but who have not completed the waitlist process. Topics for the videos will be chosen based on results of focus groups consisting of African American ESRD patients and their care givers, as well as key informant interviews with kidney healthcare providers. Once produced, the videos will be used in a feasibility study with 60 adult African American patients undergoing the pre-transplant process, determining whether the videos improve comprehension and promote positive attitudinal and behavioral readiness for transplant wait-listing.
Monocarboxylate transporters (MCTs) represent a family of 14 membrane-bound proteins, with MCTs 1-4 being primarily responsible for the transport of lactate, as well as facilitating absorption and elimination of monocarboxylate drugs. The clinical significance of MCT6 (SLC16A5) for drug transport and its endogenous function remain unknown. Currently, only bumetanide, nateglinide, and probenecid, but not lactate, have been identified as substrates in oocyte/cell studies, suggesting MCT6 is distinct from other MCT isoforms. Preliminary evidence from our lab and others have suggested a potential physiological role for MCT6: prostaglandin F2α (PGF2α) is a substrate for MCT6. Prostaglandins are long chain fatty acids and members of the eicosanoid family, having diverse hormone-like effects and playing important roles in the regulation of lipid metabolism.
The goal of our research is to understand the role of MCT6 in the transport of drugs and endogenous compounds and the potential use of MCT6 as a therapeutic target in disease. In this IMPACT grant, we will focus on understanding the role of MCT6 as a prostaglandin transporter and obtain preliminary information on its potential role as a mediator of lipid metabolism. High-throughput metabolomics/proteomics analyses on plasma, urine, and tissues from wild-type and CRISPR/Cas9-derived MCT6 knockout (KO) mouse model will be performed to identify substrates, followed by validation using in vitro X. laevis MCT6-transfected oocytes, and in vivo studies in our MCT6 KO mouse model. Our interdisciplinary team of investigators provide expertise in membrane transport, CRISPR/Cas-9 mouse and oocyte models, as well as high-throughput metabolomics and proteomic analyses.
Context: Medication harm is a major challenge for frail elders. Potentially inappropriate medications (PIMs) harm older adults, yet literature shows that PIMs are used at very high rates.
Objective: To pilot-test the translation of known medication safety evidence into primary care for frail elders through system-based interventions, including integrating pharmacist consultation into primary care (Collaborative Practice), patient/caregiver hard stop tools (Empowerment for Successful Aging), and implementing electronic systems (Health System Alerts) to disseminate patient-specific information across the system to de-prescribe harmful drugs.
Pilot Study Aims are: (1) make study-design aspects manual for a future multi-site pragmatic clinical trial; (2) generate preliminary data to assess study feasibility; and (3) estimate the effect size.
Future Design: Pragmatic cluster randomized trial using covariate constrained randomization, a design used by Practice-based Research Networks (PBRNs).One cluster of practices will implement a Collaborative Drug Safety Management (CDSM) intervention compared to another cluster using usual care.
Pilot Setting: Two primary care (PC) locations in Western New York.
Participants: 800 adults aged 65+ and their respective providers.
Intervention: The CDSM intervention will embed a pharmacist in the PC office for medication safety assessment two half-days a week, with recommendations for de-prescribing made in partnership with the patient/caregiver and shared with their provider, who provides the patient/caregiver with “hard stop” tools and issues health system alerts.
Outcome Measures: (1) Rates of de-prescribing; (2) Rates of unplanned hospitalization.
Results: We anticipate higher rates of de-prescribing and lower rates of adverse outcomes with CDSM versus usual care.
Conclusions: This study will provide pilot data leading to a series of larger intervention studies (initially NIA PAR-16-367) to address the current challenges of reducing medication harm in a fragmented healthcare system.
Under normal feeding and drinking conditions taste compounds must mix with saliva before reaching their receptor targets. Animal models have demonstrated that salivary proteins have the ability to modify the way that tastants are perceived and that exposure to certain tastants can alter the salivary protein milieu [1, 2]. There is also correlational data in humans linking the acceptance of caffeine and the expression of salivary proteins such as cystatin SN and salivary amylase . Variation in salivary protein expression therefore likely influences food acceptance.
Caffeine is a food additive that is extremely bitter. While many caffeinated beverages contain sugar to mask the bitter taste, some highly caffeinated beverages, such as coffee and energy drinks, are perceived as bitter and are often disliked upon initial exposures. As use of caffeinated products, such as energy drinks, increases among children and adolescents, it is important to understand factors that may contribute to caffeine overuse. This proposal will test two hypotheses: Hypothesis 1: Salivary protein expression will be predictive of caffeine sensitivity and preference. Hypothesis 2: Changes in salivary proteins after repeated exposure to caffeine will be associated with changes in bitterness and hedonic ratings. These experiments are the first step to a translational and collaborative R01 submission.
Plant-based medicines are essential for human health as 20% of the essential medicines listed by the World Health Organization (WHO) are derived from plants. Because these compounds are present at extremely low concentrations in their native host, the current method of farming host plants is inefficient to meet the production needs. Progress in synthetic biology has enabled massive engineering of microbes to produce plant-derived terpenoids. Examples include artemisinin for malaria, and taxol for cancer. However, there is no systematic way to improve the production of terpenoids to an industrially relevant level. We propose to build a high-titer monoterpene (10 carbons) production platform in fast-growing microbes as a cornerstone for making a myriad of medicinally important terpenes (20 to 30 carbons). Specific aims include 1, design and build a monoterpene biosynthesis pathway in microbes; 2, alleviate bottlenecks to achieve high flux.
All terpenoids are derived from the same five-carbon units that condense to mono- (C10), di- (C20), and triterpene (C30). Building a microbial platform for monoterpene synthesis opens up the opportunity to produce many medicinal terpenes at a scale that is not possible now. We expect this project to provide a sustainable and cost-effective approach for the production of plant-based medicines to increase the global healthcare equality. The project leverages the proposing team’s expertise in synthetic biology, metabolic engineering, and analytical chemistry. The award is pivotal to build the preliminary foundation to apply for the National Institute of Health (NIH) “Synthetic Biology for Engineering Applications (R01)” program.
Molybdenum disulfide (MoS2) has recently emerged as an advanced two-dimensional (2D) material that is complementary to zero-bandgap graphene. The presence of an intrinsic bandgap in monolayers with low dangling bonds population makes MoS2 a promising candidate for studying low-power consumption field-effect transistors. Recently, chemical vapor deposition (CVD), which has been used for high-quality graphene growth, has been adopted for MoS2 synthesis. Nevertheless, large-area MoS2 synthesis with controlled layer number has not been realized. Accordingly, there is a critical need to develop a standard procedure and optimized recipe for MoS2 growth using CVD.
In this proposed research, the PIs will enable smart 2D materials synthesis by proposing data and knowledge driven process design, modeling, learning and control methodologies. In particular, an advanced CVD system with real-time monitoring functions will be used as the platform for this study. A novel Bayesian D-optimal design of experiment (DOE) with mixed scalar process parameters and functional process parameters is proposed, where the prior process domain knowledge is incorporated in the design. The process input-output relationship is then learned in the empirical modeling. In addition, a systematic iterative learning control (ILC) framework will be proposed and customized to the CVD process to bridge the gap between learning/control methodologies and the CVD process. This framework will allow system to learn from previous data automatically and significantly increase the accuracy, efficiency and reduce the experimental effort. The proposed smart material growth approach can be widely applied to various materials and systems.
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